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In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

The aim of this study was to prepare inclusion nanocomplexes of hyaluronic acid-β-cyclodextrin and simvastatin (HA-β-CD/SIM) and evaluate in vitro anti-inflammation effects on lipopolysaccharide (LPS)-activated synoviocytes and chondrogenic differentiation effects on rat adipose-derived stem cells (rADSCs). The β-CD moieties in HA-β-CD could incorporate SIM to form HA-β-CD/SIM nanocomplexes with diameters of 297–350 nm. HA-β-CD/SIM resulted in long-term release of SIM from the nanocomplexes for up to 63 days in a sustained manner. In vitro studies revealed that HA-β-CD/SIM nanocomplexes were able to effectively and dose-dependently suppress the mRNA expression levels of pro-inflammatory markers such as matrix metallopeptidase-3 (MMP-3), MMP-13, cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), interleukin-6 (IL-6), and tumor necrosis factor (TNF-α) in LPS-stimulated synoviocytes. HA-β-CD/SIM-treated rADSCs significantly and dose-dependently enhanced mRNA expressions of aggrecan, collagen type II (COL2A1), and collagen type X (COL10A1), implying that HA-β-CD/SIM greatly induced the chondrogenic differentiation of rADSCs. Conclusively, HA-β-CD/SIM nanocomplexes will be a promising therapeutic material to alleviate inflammation as well as promote chondrogenesis.

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Acknowledgements

This study was supported by the grants provided by the Bio and Medical Technology Development Program of NRF funded by the Korean government, MSIP (NRF-2017M3A9F5030273 and NRF-2017M3A9B3063640) and a grant provided by the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI15C1665).

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Authors and Affiliations

  1. Department of Orthopedic Surgery, Konkuk University School of Medicine, 120-1 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, 05029, Korea

    Tae-Hoon Kim

  2. Department of Orthopedic Surgery and Rare Diseases Institute, Korea University Guro Hospital, Korea University College of Medicine, #148, Guro-dong, Guro-gu, Seoul, 08308, Korea

    Young-Pil Yun, Kyu-Sik Shim, Hak-Jun Kim, Sung Eun Kim & Hae-Ryong Song

  3. Department of Biomedical Science, Korea University College of Medicine, Korea University, Anam-dong, Seongbuk-gu, Seoul, 02841, Korea

    Kyu-Sik Shim

  4. Department of Systems Biotechnology, College of Biotechnology and Natural Resources, Chung-Ang University, 4726 Seodong-daero, Daedeok-myeon, Anseong-si, Gyeonggi-do, 17546, Korea

    Kyeongsoon Park

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  1. Tae-Hoon Kim
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Correspondence to Sung Eun Kim, Kyeongsoon Park or Hae-Ryong Song.

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Ethical statement

Animal experimental procedures were approved by the Institutional Animal Care and Use Committee of the Korea University Medical Center (KUIACUC-2014-268 and KUIACUC-2014-5).

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Kim, TH., Yun, YP., Shim, KS. et al. In Vitro Anti-Inflammation and Chondrogenic Differentiation Effects of Inclusion Nanocomplexes of Hyaluronic Acid-Beta Cyclodextrin and Simvastatin. Tissue Eng Regen Med 15, 263–274 (2018). https://doi.org/10.1007/s13770-018-0119-9

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  • DOI: https://doi.org/10.1007/s13770-018-0119-9

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